Pulmonary venous pressure increases during alveolar hypoxia in isolated lungs of newborn pigs.

The purpose of this study was to determine whether pulmonary venous pressure increases during alveolar hypoxia in lungs of newborn pigs. We isolated and perfused with blood the lungs from seven newborn pigs, 6-7 days old. We maintained blood flow constant at 50 ml.min-1.kg-1 and continuously monitored pulmonary arterial and left atrial pressures. Using the micropuncture technique, we measured pressures in 10 to 60-microns-diam venules during inflation with normoxic (21% O2-69-74% N2-5-10% CO2) and hypoxic (90-95% N2-5-10% CO2) gas mixtures. PO2 was 142 +/- 21 Torr during normoxia and 20 +/- 4 Torr during hypoxia. During micropuncture we inflated the lungs to a constant airway pressure of 5 cmH2O and kept left atrial pressure greater than airway pressure (zone 3). During hypoxia, pulmonary arterial pressure increased by 69 +/- 24% and pressure in small venules increased by 40 +/- 23%. These results are similar to those obtained with newborn lambs and ferrets but differ from results with newborn rabbits. The site of hypoxic vasoconstriction in newborn lungs is species dependent.     

PO2 modulation of paraquat-induced microvascular injury in isolated dog lungs

We determined the effects of paraquat (PQ) concentrations ranging from 10(-3) to 10(-2) M and three levels of venous PO2 [hypoxia (41 +/- 3 Torr), normoxia (147 +/- 8 Torr), and hyperoxia (444 +/- 17 Torr)] in the presence of 4 x 10(-3) M PQ on microvascular permeability in isolated blood-perfused dog lungs. Capillary filtration coefficient (Kf,c) increased and isogravimetric capillary pressure (Pc,i) decreased 3 h after perfusion with 10(-2) M PQ (n = 7) and 5 h after perfusion with 4 x 10(-3) M PQ (n = 6) but not with 10(-3) M PQ (n = 4). In hyperoxic lungs perfused with 4 x 10(-3) M PQ, Kf,c increased to nine times the base-line value 5 h after PQ [0.15 +/- 0.01 to 1.35 +/- 0.25 (SE) ml.min-1.cmH2O-1.100 g-1]. Pc,i significantly decreased from a base-line value of 9.4 +/- 0.2 to 7.1 +/- 0.4 cmH2O at 3 h. In hypoxic lungs perfused with 4 x 10(-3) M PQ (n = 5), Pc,i and Kf,c changes were not significantly different from those in normoxic lungs treated with PQ. Thus both hyperoxia and an increased dose of PQ shortened the latent period and increased the severity of the PQ-induced microvascular permeability lesion, but hypoxia failed to prevent the PQ damage.     

Microvascular pressure profile in intact in situ lung.

We measured the microvascular pressure profile in lungs physiologically expanded in the pleural space at functional residual capacity. In 29 anesthetized rabbits a caudal intercostal space was cleared of its external and internal muscles. A small area of endothoracic fascia was surgically thinned, exposing the parietal pleura through which pulmonary vessels were clearly detectable under stereomicroscopic view. Pulmonary microvascular pressure was measured with glass micropipettes connected to a servo-null system. During the pressure measurements the animal was kept apneic and 50% humidified oxygen was delivered in the trachea. Pulmonary arterial and left atrial pressures were 22.3 +/- 1.5 and 1.6 +/- 1.5 (SD) cmH2O, respectively. The segmental pulmonary vascular pressure drop expressed as a percentage of the pulmonary arterial to left atrial pressure was approximately 33% from pulmonary artery to approximately 130-microns-diam arterioles, 4.5% from approximately 130- to approximately 60-microns-diam arterioles, approximately 46% from approximately 60-microns-diam arterioles to approximately 30-microns-diam venules, approximately 9.5% from 30- to 150-microns-diam venules, and approximately 7% for the remaining venous segment. Pulmonary capillary pressure was estimated at approximately 9 cmH2O.     

Microvascular pressures during hypoxia in isolated lungs of newborn rabbits

The purpose of this study was to determine the sites of hypoxic vasoconstriction in lungs of newborn rabbits. We isolated and perfused with blood the lungs from 19 rabbit pups, 7-23 days old. We maintained blood flow constant, continuously monitored pulmonary arterial and left atrial pressures, and alternated ventilation of the lungs with 95% O2-5% CO2 (control), and 95% N2-5% CO2 (hypoxia). Using micropipettes and a servonulling device, we measured pressures in 20-60-micron-diam subpleural arterioles and venules during control and hypoxic conditions. We inflated the lungs to a constant airway pressure of 5-7 cmH2O and kept left atrial pressure greater than airway pressure (zone 3) during micropuncture. In eight lungs we measured microvascular pressures first during control and then during hypoxia. We reversed this order in four lungs. In seven lungs we measured microvascular pressures only during hypoxia. We found a significant increase in pulmonary arterial pressure with no change in microvascular pressures. These results indicate that the site of hypoxic vasoconstriction in lungs of newborn rabbits is arteries greater than 60 micron in diameter.     

Oxygen transport to exercising leg in chronic hypoxia

Residence at high altitude could be accompanied by adaptations that alter the mechanisms of O2 delivery to exercising muscle. Seven sea level resident males, aged 22 +/- 1 yr, performed moderate to near-maximal steady-state cycle exercise at sea level in normoxia [inspired PO2 (PIO2) 150 Torr] and acute hypobaric hypoxia (barometric pressure, 445 Torr; PIO2, 83 Torr), and after 18 days' residence on Pikes Peak (4,300 m) while breathing ambient air (PIO2, 86 Torr) and air similar to that at sea level (35% O2, PIO2, 144 Torr). In both hypoxia and normoxia, after acclimatization the femoral arterial-iliac venous O2 content difference, hemoglobin concentration, and arterial O2 content, were higher than before acclimatization, but the venous PO2 (PVO2) was unchanged. Thermodilution leg blood flow was lower but calculated arterial O2 delivery and leg VO2 similar in hypoxia after vs. before acclimatization. Mean arterial pressure (MAP) and total peripheral resistance in hypoxia were greater after, than before, acclimatization. We concluded that acclimatization did not increase O2 delivery but rather maintained delivery via increased arterial oxygenation and decreased leg blood flow. The maintenance of PVO2 and the higher MAP after acclimatization suggested matching of O2 delivery to tissue O2 demands, with vasoconstriction possibly contributing to the decreased flow.     

Hypoxic pulmonary vasoconstriction during steady and pulsatile flow in ferrets

We examined the effects of hypoxia and pulsatile flow on the pressure-flow relationships in the isolated perfused lungs of Fitch ferrets. When perfused by autologous blood from a pump providing a steady flow of 60 ml/min, the mean pulmonary arterial pressure rose from 14.6 to 31.3 Torr when alveolar PO2 was reduced from 122 to 46 Torr. This hypoxic pressor response was characterized by a 10.1-Torr increase in the pressure-axis intercept of the extrapolated pressure-flow curves and an increase in the slope of these curves from 130 to 240 Torr X l-1 X min. With pulsatile perfusion from a piston-type pump, mean pulmonary arterial pressure increased from 17.5 to 36.3 Torr at the same mean flow. This hypoxic pressor response was also characterized by increases in the intercept pressure and slope of the pressure-flow curves. When airway pressure was raised during hypoxia, the intercept pressure increased further to 25 +/- 1 Torr with a further increase in vascular resistance to 360 Torr X l-1 X min. Thus, in contrast to the dog lung, in the ferret lung pulsatile perfusion does not result in lower perfusion pressures during hypoxia when compared with similar mean levels of steady flow. Since the effects of high airway pressure and hypoxia are additive, they appear to act at or near the same site in elevating perfusion pressure.     

Effect of progressive exercise on lung fluid balance in sheep

The purpose of this study is to determine the roles of cardiac output and microvascular pressure on changes in lung fluid balance during exercise in awake sheep. We studied seven sheep during progressive treadmill exercise to exhaustion (10% grade), six sheep during prolonged constant-rate exercise for 45-60 min, and five sheep during hypoxia (fraction of inspired O2 = 0.12) and hypoxic exercise. We made continuous measurements of pulmonary arterial, left atrial, and systemic arterial pressures, lung lymph flow, and cardiac output. Exercise more than doubled cardiac output and increased pulmonary arterial pressures from 19.2 +/- 1 to 34.8 +/- 3.5 (SE) cmH2O. Lung lymph flow increased rapidly fivefold during progressive exercise and returned immediately to base-line levels when exercise was stopped. Lymph-to-plasma protein concentration ratios decreased slightly but steadily. Lymph flows correlated closely with changes in cardiac output and with calculated microvascular pressures. The drop in lymph-to-plasma protein ratio during exercise suggests that microvascular pressure rises during exercise, perhaps due to increased pulmonary venous pressure. Lymph flow and protein content were unaffected by hypoxia, and hypoxia did not alter the lymph changes seen during normoxic exercise. Lung lymph flow did not immediately return to base line after prolonged exercise, suggesting hydration of the lung interstitium.     

Time course of muscular blood metabolites during forearm rhythmic exercise in hypoxia

O2 concentration, PO2, PCO2, pH, osmolarity, lactate (LA), and hemoglobin (Hb) concentrations in deep forearm venous blood were repeatedly measured during submaximal exercise of forearm muscles. Concentrations of arterial blood gases were determined at rest and during exercise. Experiments were conducted under normoxia and hypobaric hypoxia (PB = 465 Torr). In arterial blood, data obtained during exercise were the same as those obtained during rest under either normoxia or hypoxia. In venous muscular blood, PO2 and O2 concentration were lower at rest and during exercise in hypoxia. The muscular arteriovenous O2 difference during exercise in hypoxia was increased by no more than 10% compared with normoxia, which implied that muscular blood flow during exercise also increased by the same percentage, if we assume that exercise O2 consumption was not affected by hypoxia. Despite increased [LA], the magnitude of changes in PCO2 and pH in hypoxia were smaller than in normoxia during exercise and recovery; this finding is probably due to the increased blood buffer value induced by the greater amount of reduced Hb in hypoxia. Hence all the changes occurring in hypoxia showed that local metabolism was less affected than we expected from the decrease in arterial PO2. The rise in [Hb] that occurred during exercise was lower in hypoxia. Possible underlying mechanisms of the [Hb] rise during exercise are discussed.     

Microvascular pressures measured by micropuncture in lungs of newborn rabbits

The purpose of this study was to determine the pattern of vascular pressure drop in newborn lungs and to define the contribution of active vasomotor tone to this longitudinal pressure profile. We isolated and perfused with blood the lungs from 22 rabbit pups, 5-19 days old. We inflated the lungs to a constant airway pressure of 7 cmH2O, and at constant blood flow, we maintained outflow pressure in the circulation greater than airway pressure at the level of micropuncture (zone 3). By the use of glass micropipettes and a servo-nulling device, we measured pressures in small (20-60 micron diam) subpleural arterioles and venules in the lungs of 13 newborn rabbits. We found that 60% of the pressure drop was in arteries, 31% in microvessels of less than 20-60 micron diam, and 9% in veins. In the lungs of an additional nine rabbit pups we measured microvascular pressures before and after the addition to the perfusate of the vasodilator, papaverine hydrochloride. We found that removal of vasomotor tone resulted in a 33% reduction in total lung vascular resistance, which resulted from a decrease in pressure in arterial vessels, with no change in microvascular pressure. These findings indicate that arteries of greater than 60 micron diam constitute the major source of vascular resistance in isolated perfused newborn rabbit lungs.     

Ventilatory effects and interactions with change in PaO2 in awake goats.

We utilized selective carotid body (CB) perfusion while changing inspired O2 fraction in arterial isocapnia to characterize the non-CB chemoreceptor ventilatory response to changes in arterial PO2 (PaO2) in awake goats and to define the effect of varying levels of CB PO2 on this response. Systemic hyperoxia (PaO2 greater than 400 Torr) significantly increased inspired ventilation (VI) and tidal volume (VT) in goats during CB normoxia, and systemic hypoxia (PaO2 = 29 Torr) significantly increased VI and respiratory frequency in these goats. CB hypoxia (CB PO2 = 34 Torr) in systemic normoxia significantly increased VI, VT, and VT/TI; the ventilatory effects of CB hypoxia were not significantly altered by varying systemic PaO2. We conclude that ventilation is stimulated by systemic hypoxia and hyperoxia in CB normoxia and that this ventilatory response to changes in systemic O2 affects the CB O2 response in an additive manner.     

Shivering and cardiorespiratory responses during normocapnic hypoxia in the pigeon

To study the inhibitory effect of hypoxia on the cold defense mechanism, pigeons were exposed at low ambient temperature (5 degrees C) to various inhaled gas mixtures: normoxia [0.21 fractional concentration of O2 (FIO2)], hypoxia (0.07 FIO2), and normocapnic hypoxia (0.07 FIO2 + 0.045 FICO2). Electromyographic (EMG) activity indicative of shivering thermogenesis was inhibited during hypoxia, and body temperature (Tre) fell by 0.09 degrees C/min. Respiratory frequency (f) and minute ventilation (VE) increased by 143 and 135%, respectively, compared with normoxia, but tidal volume (VT) was not changed. PO2, PCO2, and O2 contents in the arterial and mixed venous blood were decreased and pH was enhanced. During normocapnic hypoxia, shivering EMG was present at approximately 50% of the normoxic intensity; Tre fell by only 0.04 degrees C/min. Arterial and mixed venous PCO2 and pH were the same as during normoxia, but VE increased by 430% because of twofold increases in both f and VT. During normocapnic hypoxia, arterial PO2 and O2 content were higher than during hypoxia alone. We conclude that the persistence of shivering during normocapnic hypoxia is due to maintenance of critical levels of arterial PO2 and O2 content.     

Nature and distribution of vascular resistance in hypoxic pig lungs

We used the vascular occlusion technique in pig lungs isolated in situ to describe the effects of hypoxia on the distribution of vascular resistance and to determine whether the resistive elements defined by this technique behaved as ohmic or Starling resistors during changes in flow at constant outflow pressure, changes in outflow pressure at constant flow, and reversal of flow. During normoxia, the largest pressure gradient occurred across the middle compliant region of the vasculature (delta Pm). The major effect of hypoxia was to increase delta Pm and the gradient across the relatively noncompliant arterial region (delta Pa). The gradient across the noncompliant venous region (delta Pv) changed only slightly, if at all. Both delta Pa and delta Pv increased with flow but delta Pm decreased. The pressure at the arterial end of the middle region was independent of flow and, when outflow pressure was increased, did not increase until the outflow pressure of the middle region exceeded 8.9 Torr during normoxia and 18.8 Torr during hypoxia. Backward perfusion increased the total pressure gradient across the lung, mainly because of an increase in delta Pm. These results can be explained by a model in which the arterial and venous regions are represented by ohmic resistors and the middle region is represented by a Starling resistor in series and proximal to an ohmic resistor. In terms of this model, hypoxia exerted its major effects by increasing the critical pressure provided by the Starling resistor of the middle region and the ohmic resistance of the arterial region.     

Adenosine A2A-receptor blockade abolishes the roll-off respiratory response to hypoxia in awake lambs

Adenosine (ADO) receptor antagonists (aminophylline, caffeine) blunt the respiratory roll-off response to hypoxia in the newborn. This study was designed to determine the ADO receptor subtype involved in the respiratory depression. Chronically catheterized lambs of 7-16 days of age breathed via face mask a gas mixture with a fraction of inspired O2 of 0.21 (normoxia) or 0.07 (hypoxia), while being infused intravascularly with 9-cyclopentyl-1,3-dipropylxanthine (DPCPX; ADO A1-receptor antagonist, n=8), ZM-241385 (ADO A2A-receptor antagonist, n=7), or vehicle. Ventilation was measured at 20 degrees C by a turbine transducer flowmeter. In normoxia [arterial Po2 (PaO2) of approximately 83 Torr], infusion of vehicle did not alter cardiorespiratory measurements, whereas hypoxia (PaO2 of approximately 31 Torr, 15 min) elicited biphasic effects on mean arterial pressure (transient increase), heart rate (HR; diminishing tachycardia), and minute ventilation. In the latter, hypoxia increased ventilation to a peak value of approximately 2.5 times control within the first 3 min, which was followed by a significant (P<0.05) decline to approximately 50% of the maximum increment over the subsequent 7 min. ZM-241385 abolished the hypoxic ventilatory roll-off and blunted the rate of rise in HR without affecting mean arterial pressure or rectal temperature responses. In normoxia, DPCPX increased ventilation and mean arterial pressure but did not change HR. Compared with vehicle, DPCPX did not significantly affect cardiorespiratory responses to hypoxemia (PaO2 of approximately 31 Torr, 10 min). It is concluded that 1) ADO A2A receptors are critically involved in the ventilatory roll-off and HR responses to hypoxia, and 2) ADO A1 receptors, which are tonically active in cardiorespiratory control in normoxia, appear to have little impact on hypoxic ventilatory depression.     

Role of hemoglobin P50 in O2 transport during normoxic and hypoxic exercise in the dog

High hemoglobin affinity for O2 [low PO2 at 50% saturation of hemoglobin (P50)] could degrade exercise performance in normoxia by lowering mean tissue PO2 but could enhance O2 transport in hypoxic exercise by increasing arterial O2 saturation. We measured O2 transport at rest and at graded levels of steady-state exercise in tracheostomized dogs with normal P50 (28.8 +/- 1.8 Torr) and again after P50 was lowered (19.5 +/- 0.7 Torr) by sodium cyanate infusions. Measurements were made during ventilation with room air (RA), 12% O2 in N2, or 10% O2 in N2. Cardiac output (QT) as a function of O2 consumption (VO2) was not altered by low P50 at any inspired O2 fraction (P greater than 0.05). With RA exercise, arterial content (CaO2) and O2 delivery (QT X CaO2) were unchanged at low P50, whereas mixed venous PO2 was reduced at each level of VO2. With exercise in hypoxia, CaO2 and O2 delivery were significantly improved at low P50 (P less than 0.05). Mixed venous PO2 was lower than control during 12% O2 (P less than 0.05) but not different from control during 10% O2 exercise at low P50. Despite a presumed decrease in tissue PO2 during RA and 12% O2 exercise, exercise performance and base excess decline were not significantly worse than control levels. We conclude that, in canine steady-state exercise, hemoglobin P50 is not an important determinant of tissue O2-extraction capacity during normoxia or moderate hypoxia. In extreme hypoxia, low P50 may help to maintain tissue PO2 by enhancing systemic O2 delivery at each level of QT.     

Microvascular pressures measured by micropuncture in isolated perfused lamb lungs

To investigate the influence of vasomotor tone and vessel compliance on pulmonary segmental vascular resistance, we determined the longitudinal distribution of vascular pressures in 15 isolated blood perfused lungs of newborn lambs. We measured pulmonary arterial and left atrial pressures and by micropuncture the pressures in 20- to 80-micron-diam subpleural arterioles and venules, both before and after paralyzing the vasculature with papaverine hydrochloride. In five lungs we also determined the microvascular pressure profile during reverse perfusion. In lungs with baseline vasomotor tone, approximately 32% of the total pressure drop was in arteries, approximately 32% in microvessels, and approximately 36% in veins. With elimination of vasomotor tone, arterial and venous resistances decreased to one-fifth and one-half of base-line values, respectively, indicating that vasomotor tone contributed mainly toward arterial resistance. During reverse perfusion, the pressure drop in veins was similar to that in arteries during forward perfusion, suggesting that the compliance of arteries and veins is comparable. We conclude that vascular tone and compliance are important factors that determine the distribution of segmental vascular resistance in lungs of the newborn.     

Maximum oxygen uptake and arterial blood oxygenation during hypoxic exercise in rats.

The objectives of these experiments were 1) to describe the effect of maximum treadmill exercise on gas exchange, arterial blood gases, and arterial blood oxygenation in rats acclimated for 3 wk to simulated altitude (SA, barometric pressure 370-380 Torr) and 2) to determine the contribution of acid-base changes to the changes in arterial blood oxygenation of hypoxic exercise. Maximum O2 uptake (VO2max) was measured in four groups of rats: 1) normoxic controls run in normoxia (Nx), 2) normoxic controls run in acute hypoxia [AHx inspiratory PO2 (PIO2) approximately 70 Torr], 3) SA rats run in hypoxia (3WHx, PIO2 approximately 70 Torr), and 4) SA rats run in normoxia (ANx). VO2max (ml STPD.min-1.kg-1) was 70.8 +/- 0.9 in Nx, 46.4 +/- 1.9 in AHx, 52.6 +/- 1.1 in 3WHx, and 70.0 +/- 2.4 in ANx. Exercise resulted in acidosis, hypocapnia, and elevated blood lactate in all groups. Although blood lactate increased less in 3WHx and ANx, pH was the same or lower than in Nx and AHx, reflecting the low buffer capacity of SA. In AHx and 3WHx, arterial PO2 increased with exercise; however, O2 saturation of hemoglobin in arterial blood (SaO2) decreased. In vitro measurements of the Bohr shift suggest that SaO2 decreased as a result of a decrease in hemoglobin O2 affinity. The data indicate that several features of hypoxic exercise in this model are similar to those seen in humans, with the exception of the mechanism of decrease in SaO2, which, in humans, appears to be due to incomplete alveolar-capillary equilibration.     

Flow-volume characteristics in the pulmonary circulation

Isolated ferret and canine lungs were used to validate a method for assessing determinants of vascular volume in the pulmonary circulation. With left atrial pressure (Pla) constant at 5 mmHg, flow (Q) was raised in steps over a physiological range. Changes in vascular volume (delta V) with each increment in Q were determined as the opposite of changes in perfusion system reservoir weight or from the increase in lung weight. At each level of Q, the pulmonary arterial and left atrial cannulas were simultaneously occluded, allowing all vascular pressures to equilibrate at the same static pressure (Ps), which was equal to the compliance-weighted average pressure in the circulation before occlusion. Hypoxia (inspired PO2 25 Torr) in ferret lungs, which causes intense constriction in arterial extra-alveolar vessels, had no effect on the slope of the Ps-Q relationship, interpreted to represent the resistance downstream from compliance (control 0.025 +/- 0.006 mmHg.ml-1.min, hypoxia 0.030 +/- 0.013). The Ps-axis intercept increased from 8.94 +/- 0.50 to 13.43 +/- 1.52 mmHg, indicating a modest increase in the effective back-pressure to flow downstream from compliant regions. The compliance of the circulation, obtained from the slope of the relationship between delta V and Ps, was unaffected by hypoxia (control 0.52 +/- 0.08 ml/mmHg, hypoxia 0.56 +/- 0.08). In contrast, histamine in canine lungs, which causes constriction in veins, caused the slope of the Ps-Q relationship to increase from 0.013 +/- 0.007 to 0.032 +/- 0.006 mmHg.ml-1.min (P less than 0.05) and the compliance to decrease from 3.51 +/- 0.56 to 1.68 +/- 0.37 ml/mmHg (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Pulmonary interstitial pressure and tissue matrix structure in acute hypoxia

Pulmonary interstitial pressure was measured via micropuncture in anesthetized rabbits in normoxia and after breathing 12% O(2). In normoxia [arterial PO(2) = 88 +/- 2 (SD) mmHg], pulmonary arterial pressure and pulmonary interstitial pressure were 16 +/- 8 and -9.6 +/- 2 cmH(2)O, respectively. After 6 h of hypoxia (arterial PO(2) = 39 +/- 16 mm Hg), the corresponding values were 30+/-8 and 3.5+/-2.5 cm H(2)O (P<0.05). Pulmonary interstitial proteoglycan extractability, evaluated by hexuronate assay after 0.4 M guanidinium hydrochloride extraction, was 12.3, 32.4, and 60.6 microg/g wet tissue in normoxia and after 3 and 6 h of hypoxia, respectively, indicating a weakening of the noncovalent bonds linking proteoglycans to other extracellular matrix components. Gel filtration chromatography showed an increased fragmentation of chondroitin sulfate- and heparan sulfate-proteoglycans during hypoxic exposure, accounting for a loss of extracellular matrix native architecture and basement membrane structure. Gelatin zymography demonstrated increased amounts of the proteolytically activated form of gelatinase B (matrix metalloproteinase-9) after hypoxic exposure, providing evidence that the activation of proteinases may play a role in hypoxia-induced lung injury.     

Ventilatory response to moderate and severe hypoxia in adult dogs: role of endorphins

To determine the role of opioids in modulating the ventilatory response to moderate or severe hypoxia, we studied ventilation in six chronically instrumented awake adult dogs during hypoxia before and after naloxone administration. Parenteral naloxone (200 micrograms/kg) significantly increased instantaneous minute ventilation (VT/TT) during severe hypoxia, (inspired O2 fraction = 0.07, arterial PO2 = 28-35 Torr); however, consistent effects during moderate hypoxia (inspired O2 fraction = 0.12, arterial PO2 = 40-47 Torr) could not be demonstrated. Parenteral naloxone increased O2 consumption (VO2) in severe hypoxia as well. Despite significant increases in ventilation post-naloxone during severe hypoxia, arterial blood gas tensions remained the same. Control studies revealed that neither saline nor naloxone produced a respiratory effect during normoxia; also the preservative vehicle of naloxone induced no change in ventilation during severe hypoxia. These data suggest that, in adult dogs, endorphins are released and act to restrain ventilation during severe hypoxia; the relationship between endorphin release and moderate hypoxia is less consistent. The observed increase in ventilation post-naloxone during severe hypoxia is accompanied by an increase in metabolic rate, explaining the isocapnic response.     

Effects of acute hypoxia and CO2 inhalation on systemic and peripheral oxygen uptake and circulatory responses during moderate exercise

The effect of acute hypoxia and CO2 inhalation on leg blood flow (LBF), on leg vascular resistance (LVR) and on oxygen supply to and oxygen consumption in the exercising leg was studied in nine healthy male subjects during moderate one-leg exercise. Each subject exercised for 20 min on a cycle ergometer in four different conditions: normoxia, normoxia + 2% CO2, hypoxia corresponding to an altitude of 4000 m above sea level, and hypoxia + 1.2% CO2. Gas exchange, heart rate (HR), arterial blood pressure, and LBF were measured, and arterial and venous blood samples were analysed for PCO2, PO2, oxygen saturation, haematocrit and haemoglobin concentration. Systemic oxygen consumption was 1.83 l.min-1 (1.48-2.59) and was not affected by hypoxia or CO2 inhalation in hypoxia. HR was unaffected by CO2, but increased from 136 beat.min-1 (111-141) in normoxia to 155 (139-169) in hypoxia. LBF was 6.5 l.min-1 (5.4-7.6) in normoxia and increased significantly in hypoxia to 8.4 (5.9-10.1). LVR decreased significantly from 2.23 kPa.l-1.min (1.89-2.99) in normoxia to 1.89 (1.53-2.52) in hypoxia. The increase in LBF from normoxia to hypoxia correlated significantly with the decrease in LVR. When CO2 was added in hypoxia a significant correlation was also found between the decrease in LBF and the increase in LVR. In normoxia, the addition of CO2 caused a significant increase in mean blood pressure. Oxygen consumption in the exercising leg (leg VO2) in normoxia was 0.97 l.min-1 (0.72-1.10), and was unaffected by hypoxia and CO2.(ABSTRACT TRUNCATED AT 250 WORDS)